Genetic association of KCNJ10 rs1130183 with seizure susceptibility and computational analysis of deleterious non-synonymous SNPs of KCNJ10 gene

Nagaraja M. Phani, Shreeshakala Acharya, Seethu Xavy, Nalini Bhaskaranand, Manoj K. Bhat, Aditya Jain, Padmalatha S. Rai, Satyamoorthy Kapaettu

Research output: Contribution to journalArticle

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Abstract

Establishing genetic basis of Idiopathic generalized epilepsies (IGE) is challenging because of their complex inheritance pattern and genetic heterogeneity. Kir4.1 inwardly rectifying channel (KCNJ10) is one of the independent genes reported to be associated with seizure susceptibility. In the current study we have performed a comprehensive in silico analysis of genetic variants in KCNJ10gene at functional and structural level along with a case-control analysis for the association ofrs1130183 (R271C) polymorphism in Indian patients with IGE. Age and sex matched 108epileptic patients and normal healthy controls were examined. Genotyping of KCNJ10rs1130183variation was performed using PCR-RFLP method. The risk association was determined by using odds ratio and 95% confidence interval. Functional effects of non-synonymous SNPs (nsSNPs) in KCNJ10 gene were analyzed using SIFT PolyPhen-2, I-Mutant 2.0, PANTHER and FASTSNP. Subsequently, homology modeling of protein three dimensional (3D) structures was performed using Modeller tool (9.10v) and compared the native protein with mutant for assessment of structure and stability. SIFT, PolyPhen-2, I-Mutant 2.0 and PANTHER collectively showed rs1130183, rs1130182 and rs137853073 SNPs in. KCNJ10 gene affect protein structure and function. There was a considerable variation in the Root Mean Square Deviation (RMSD) value between the native and mutant structure (1.17Ǻ). Association analysis indicate KCNJ10rs1130183 did not contribute to risk of seizure susceptibility in Indian patients with IGE (OR- 0.38; 95%CI, 0.07-2.05) and T allele frequency (0.02%) was in concordance with dbSNP reports. This study identifies potential SNPs that may contribute to seizure susceptibility and further studies with the selected SNPs in larger number of samples and their functional analysis is required for understanding the variants of KCNJ10with seizure susceptibility.

Original languageEnglish
Pages (from-to)247-253
Number of pages7
JournalGene
Volume536
Issue number2
DOIs
Publication statusPublished - 25-02-2014

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Single Nucleotide Polymorphism
Seizures
Genes
Inheritance Patterns
Genetic Heterogeneity
Mutant Proteins
Gene Frequency
Restriction Fragment Length Polymorphisms
Computer Simulation
Proteins
Odds Ratio
Confidence Intervals
Polymerase Chain Reaction
Idiopathic Generalized Epilepsy

All Science Journal Classification (ASJC) codes

  • Medicine(all)
  • Genetics

Cite this

Phani, Nagaraja M. ; Acharya, Shreeshakala ; Xavy, Seethu ; Bhaskaranand, Nalini ; Bhat, Manoj K. ; Jain, Aditya ; Rai, Padmalatha S. ; Kapaettu, Satyamoorthy. / Genetic association of KCNJ10 rs1130183 with seizure susceptibility and computational analysis of deleterious non-synonymous SNPs of KCNJ10 gene. In: Gene. 2014 ; Vol. 536, No. 2. pp. 247-253.
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abstract = "Establishing genetic basis of Idiopathic generalized epilepsies (IGE) is challenging because of their complex inheritance pattern and genetic heterogeneity. Kir4.1 inwardly rectifying channel (KCNJ10) is one of the independent genes reported to be associated with seizure susceptibility. In the current study we have performed a comprehensive in silico analysis of genetic variants in KCNJ10gene at functional and structural level along with a case-control analysis for the association ofrs1130183 (R271C) polymorphism in Indian patients with IGE. Age and sex matched 108epileptic patients and normal healthy controls were examined. Genotyping of KCNJ10rs1130183variation was performed using PCR-RFLP method. The risk association was determined by using odds ratio and 95{\%} confidence interval. Functional effects of non-synonymous SNPs (nsSNPs) in KCNJ10 gene were analyzed using SIFT PolyPhen-2, I-Mutant 2.0, PANTHER and FASTSNP. Subsequently, homology modeling of protein three dimensional (3D) structures was performed using Modeller tool (9.10v) and compared the native protein with mutant for assessment of structure and stability. SIFT, PolyPhen-2, I-Mutant 2.0 and PANTHER collectively showed rs1130183, rs1130182 and rs137853073 SNPs in. KCNJ10 gene affect protein structure and function. There was a considerable variation in the Root Mean Square Deviation (RMSD) value between the native and mutant structure (1.17Ǻ). Association analysis indicate KCNJ10rs1130183 did not contribute to risk of seizure susceptibility in Indian patients with IGE (OR- 0.38; 95{\%}CI, 0.07-2.05) and T allele frequency (0.02{\%}) was in concordance with dbSNP reports. This study identifies potential SNPs that may contribute to seizure susceptibility and further studies with the selected SNPs in larger number of samples and their functional analysis is required for understanding the variants of KCNJ10with seizure susceptibility.",
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Genetic association of KCNJ10 rs1130183 with seizure susceptibility and computational analysis of deleterious non-synonymous SNPs of KCNJ10 gene. / Phani, Nagaraja M.; Acharya, Shreeshakala; Xavy, Seethu; Bhaskaranand, Nalini; Bhat, Manoj K.; Jain, Aditya; Rai, Padmalatha S.; Kapaettu, Satyamoorthy.

In: Gene, Vol. 536, No. 2, 25.02.2014, p. 247-253.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genetic association of KCNJ10 rs1130183 with seizure susceptibility and computational analysis of deleterious non-synonymous SNPs of KCNJ10 gene

AU - Phani, Nagaraja M.

AU - Acharya, Shreeshakala

AU - Xavy, Seethu

AU - Bhaskaranand, Nalini

AU - Bhat, Manoj K.

AU - Jain, Aditya

AU - Rai, Padmalatha S.

AU - Kapaettu, Satyamoorthy

PY - 2014/2/25

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N2 - Establishing genetic basis of Idiopathic generalized epilepsies (IGE) is challenging because of their complex inheritance pattern and genetic heterogeneity. Kir4.1 inwardly rectifying channel (KCNJ10) is one of the independent genes reported to be associated with seizure susceptibility. In the current study we have performed a comprehensive in silico analysis of genetic variants in KCNJ10gene at functional and structural level along with a case-control analysis for the association ofrs1130183 (R271C) polymorphism in Indian patients with IGE. Age and sex matched 108epileptic patients and normal healthy controls were examined. Genotyping of KCNJ10rs1130183variation was performed using PCR-RFLP method. The risk association was determined by using odds ratio and 95% confidence interval. Functional effects of non-synonymous SNPs (nsSNPs) in KCNJ10 gene were analyzed using SIFT PolyPhen-2, I-Mutant 2.0, PANTHER and FASTSNP. Subsequently, homology modeling of protein three dimensional (3D) structures was performed using Modeller tool (9.10v) and compared the native protein with mutant for assessment of structure and stability. SIFT, PolyPhen-2, I-Mutant 2.0 and PANTHER collectively showed rs1130183, rs1130182 and rs137853073 SNPs in. KCNJ10 gene affect protein structure and function. There was a considerable variation in the Root Mean Square Deviation (RMSD) value between the native and mutant structure (1.17Ǻ). Association analysis indicate KCNJ10rs1130183 did not contribute to risk of seizure susceptibility in Indian patients with IGE (OR- 0.38; 95%CI, 0.07-2.05) and T allele frequency (0.02%) was in concordance with dbSNP reports. This study identifies potential SNPs that may contribute to seizure susceptibility and further studies with the selected SNPs in larger number of samples and their functional analysis is required for understanding the variants of KCNJ10with seizure susceptibility.

AB - Establishing genetic basis of Idiopathic generalized epilepsies (IGE) is challenging because of their complex inheritance pattern and genetic heterogeneity. Kir4.1 inwardly rectifying channel (KCNJ10) is one of the independent genes reported to be associated with seizure susceptibility. In the current study we have performed a comprehensive in silico analysis of genetic variants in KCNJ10gene at functional and structural level along with a case-control analysis for the association ofrs1130183 (R271C) polymorphism in Indian patients with IGE. Age and sex matched 108epileptic patients and normal healthy controls were examined. Genotyping of KCNJ10rs1130183variation was performed using PCR-RFLP method. The risk association was determined by using odds ratio and 95% confidence interval. Functional effects of non-synonymous SNPs (nsSNPs) in KCNJ10 gene were analyzed using SIFT PolyPhen-2, I-Mutant 2.0, PANTHER and FASTSNP. Subsequently, homology modeling of protein three dimensional (3D) structures was performed using Modeller tool (9.10v) and compared the native protein with mutant for assessment of structure and stability. SIFT, PolyPhen-2, I-Mutant 2.0 and PANTHER collectively showed rs1130183, rs1130182 and rs137853073 SNPs in. KCNJ10 gene affect protein structure and function. There was a considerable variation in the Root Mean Square Deviation (RMSD) value between the native and mutant structure (1.17Ǻ). Association analysis indicate KCNJ10rs1130183 did not contribute to risk of seizure susceptibility in Indian patients with IGE (OR- 0.38; 95%CI, 0.07-2.05) and T allele frequency (0.02%) was in concordance with dbSNP reports. This study identifies potential SNPs that may contribute to seizure susceptibility and further studies with the selected SNPs in larger number of samples and their functional analysis is required for understanding the variants of KCNJ10with seizure susceptibility.

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